Owing to the scientific and economic importance, the antagonistic wheat-Puccinia striiformis f. sp. tritici (Pst) pathosystem has been a focus of research over the past five decades. With the recent discovery of barberry as alternate hosts, Pst has been confirmed to be heteroecious, and the roles of the alternate hosts in disease epidemiology and pathogen variation have been studied. Meanwhile, considerable effort has been taken and significant progress has been made to unravel the wheat-Pst interactions. Histological and cytological studies have provided basic information on infection strategies used by the pathogen and defense responses from the host during wheat-Pst interactions and identified cellular components involved in the interactions. Physiological studies demonstrated the essential changes in Pst infected wheat leaves, unraveling the damage of the pathogen and the countermeasures of the host plants. Transcriptome and genome sequencing has revealed the molecular features and dynamics of the wheat-Pst pathosystem. Extensive molecular analyses have led to the identification of major components in the wheat resistance responses. Studies of wheat-Pst interactions have now entered a new phase in which cellular and molecular approaches are being used. In this chapter, we present the achievements made in the histological and cytological study of wheat-Pst interactions as well as physiological plant pathology. Furthermore, the new insights into wheat immunity provided by the sequence resources and advanced genomic technologies were discussed. Overall, this chapter focuses on the cellular biology of the stripe rust fungus and the wheat-Pst interactions, and integrates the emerging data from molecular analyses with the histocytological observations.